Peripheral blood mitochondrial DNA copy number is a potential biomarker for progress of diabetic nephropathy in type 2 diabetes patients

Abstract

Mitochondrial DNA (mtDNA) copy number is a surrogate measure of mitochondrial function, and altered mtDNA copy number has been associated with diabetic nephropathy (DN), a leading cause end stage renal disease in diabetic patients. We investigated whether mtDNA copy number in peripheral blood could be utilized as a biomarker for DN progress in type 2 diabetes (T2D) patients. A total of 50 non-diabetic and 100 diabetic subjects were recruited. The diabetic subjects were sub-divided based on urinary albumin-creatinine ratio (ACR) into T2D patients with normoalbuminuria (ACR < 30 mg/g, n = 50), DN patients with microalbuminuria (ACR 30–300 mg/g, n = 29), and DN patients with macroalbuminuria (ACR > 300 mg/g, n = 21). The mtDNA copy number was measured as relative quantity of mtDNA compared to nuclear DNA using real-time PCR. Overall, the mtDNA copy number was lower in T2D and DN patients than in controls (P < 0.001). Sub-group analyses by ACR showed that lower mtDNA copy number was significantly associated with high levels of albuminuria even after adjusting for conventional risk factors (odds ratio [OR] 0.47, confidence interval [CI] 0.299–0.74 for microalbuminuria and OR 0.21, 95% CI 0.1–0.436 for macroalbuminuria). Moreover, mtDNA copy number was correlated negatively with albuminuria (r = −0.546) and positively with glomerular filtration rate (r = 0.572). The areas under the receiver operating characteristic curves (AUCs) of mtDNA copy number in discriminating DN patients from T2D patients and healthy controls were 0.80 (P < 0.001) and 0.885 (P < 0.001), respectively. Our results showed that peripheral blood mtDNA copy number was associated with the development of DN and could serve as a biomarker during DN progression.